ISSN: 2148-4902 | E-ISSN: 2536-4553
Necroptosis mediated by receptor interacting protein kinase 3 as critical players in experimental congenital hypothyroidism related neuronal damage [North Clin Istanb]
North Clin Istanb. 2021; 8(5): 472-478 | DOI: 10.14744/nci.2021.26043

Necroptosis mediated by receptor interacting protein kinase 3 as critical players in experimental congenital hypothyroidism related neuronal damage

Gulhan Duman1, Mehmet Eray Alcigir2, Hayrettin Yavuz3
1Department of Endocrinology and Metabolic Disorders, Sivas Cumhuriyet University Faculty of Medicine, Sivas, Turkey
2Department of Pathology, Kirikkale University Faculty of Veterinary Medicine, Kirikkale, Turkey
3Department of Biochemistry, Sivas Cumhuriyet University Faculty of Medicine, Sivas, Turkey

OBJECTIVE: Congenital hypothyroidism (CH) is literally described as congenital thyroid hormone imperfection. The primary objective of this research was to reveal the possible relation between receptor-acting protein kinase 3 (RIPK3) activity and neuronal damages in rat pups with CH. In addition, we evaluated the favorable impacts of 3.6-dibromo-α-([phenylamino] methyl)-9H-carbazole-9-ethanol (P7C3) reducing RIPK3 activity.
METHODS: Adult rats were accordingly assigned into four groups: Group 1, which is called congenital hypothyroid; Group 2, which is called congenital hypothyroid administered P7C3; Group 3, called CH administered P7C3 and L-thyroxine; and Group 4, control group. RIPK3 level in plasma concentration and its expression in tissue was determined in all groups.
RESULTS: Increased RIPK3 expressions were detected as high in the CH group when it is compared to the control group. Furthermore; the expressions in neuronal cytoplasm were found similar among Groups II and III. RIPK3 expressions in those two groups were relatively higher than in the control group. Most reacted parts of the brain were especially Purkinje cells in the cerebellum.
CONCLUSION: It is concluded that there is excellent parallelism among damaged neurons and high RIPK3 activity in CH pathogenesis. P7C3 compounds may have a safeguarding impact on CH due to decreasing RIPK3 activity.

Keywords: Congenital hypothyroidism, rat; receptor-acting protein kinase 3 activity; 3.6-Dibromo-α-([phenylamino] methyl)-9H-carbazole-9-ethanol.

Necroptosis mediated by receptor interacting protein kinase 3 as critical player in experimental congenital hypothyroidism related neuronal damage

Gulhan Duman1, Mehmet Eray Alcigir2, Hayrettin Yavuz3
1Sivas Cumhuriyet Üniversitesi Tıp Fakültesi, Endokrinoloji ve Metabolik Bozukluklar Anabilim Dalı, Sivas
2Kırıkkale Üniversitesi, Veteriner Fakültesi, Patoloji Anabilim Dalı, Kırıkkale
3Sivas Cumhuriyet Üniversitesi Tıp Fakültesi Biyokimya Anabilim Dalı, Sivas

Objektif: Konjenital hipotiroidizm (KH) doğuştan tiroid hormonu kusuru olarak tanımlanmaktadır. Bu araştırmanın birincil amacı, KH'li sıçan yavrularında RIPK3 aktivitesi ile nöronal hasarlar arasındaki olası ilişkiyi ortaya çıkarmaktır. Yanısıra 3,6-Dibromo-α - [(fenilamino)metil]-9H-karbazol-9-etanolün (P7C3) RIPK3 aktivitesini azaltan etkiler incelendi.
Materyal ve Metod: Erişkin sıçanlar dört gruba ayrıldı: Grup 1, konjenital hipotiroidi; Grup 2, konjenital hipotiroid uygulanan P7C3; Grup 3, KH uygulanan P7C3 ve L-tiroksin; Grup 4, kontrol grubu. Plazma konsantrasyonundaki ve dokudaki RIPK3 düzeyi ve gen ekspresyon seviyesi tüm gruplarda incelendi.
Bulgular: Kontrol grubu ile karşılaştırıldığında CH grubunda artan RIPK3 ekspresyonları yüksek olarak bulundu. Ayrıca; Nöronal sitoplazmadaki ifadeler grup II ve III arasında benzer bulundu. Bu iki gruptaki RIPK3 ifadeleri, kontrol grubuna göre nispeten daha yüksekti. Beynin en çok tepki veren kısımları, özellikle serebellumdaki Purkinje hücreleriydi.
Sonuç: KH patogenezinde hasarlı nöronlar arasında mükemmel paralellik ve yüksek RIPK3 aktivitesi olduğu sonucuna varıldı. P7C3 bileşikleri, RIPK3 aktivitesinin azalması nedeniyle KH üzerinde koruyucu bir etkiye sahip olabilir. (NCI-2021-3-11)

Anahtar Kelimeler: Konjenital hipotiroidizm, RIPK3 aktivitesi, P7C3, sıçan

Gulhan Duman, Mehmet Eray Alcigir, Hayrettin Yavuz. Necroptosis mediated by receptor interacting protein kinase 3 as critical players in experimental congenital hypothyroidism related neuronal damage. North Clin Istanb. 2021; 8(5): 472-478

Corresponding Author: Gulhan Duman
Manuscript Language: English
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